腸管バリア(リーキーガット)を改善する108の方法(作成中)

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腸管透過性と食品・サプリメント・乳酸菌

腸管透過性の改善

概日リズムの最適化

腸の機能は概日リズム変動に従って活動する。マウスの実験において遺伝的、環境的変化による概日リズムを破壊は、タイトジャンクションタンパク質オクルディンを介してリーキーガットを引き起こすことが示されている。

Disruption of the Circadian Clock in Mice Increases Intestinal Permeability and Promotes Alcohol-Induced Hepatic Pathology and Inflammation
The circadian clock orchestrates temporal patterns of physiology and behavior relative to the environmental light:dark cycle by generating and organizing transc

ダイエット

FODMAPダイエット

食物の吸収性が低い短鎖炭水化物は、近位結腸への水分および発酵性基質の送達を増加させる。

Dietary Poorly Absorbed, Short-Chain Carbohydrates Increase Delivery of Water and Fermentable Substrates to the Proximal Colon - PubMed
These data support the hypothetical mechanism; FODMAPs increase delivery of water and fermentable substrates to the proximal colon.
Diets With High or Low Protein Content and Glycemic Index for Weight-Loss Maintenance - PubMed
In this large European study, a modest increase in protein content and a modest reduction in the glycemic index led to an improvement in study completion and ma

食品

ナツメグ・ベイリーフ

黒コショウ(パイパー)、ピーマン、ナツメグ、およびベイリーフ抽出物は、TEERの増加を引き起こしたが、小分子の透過性およびZO-1の組織化は影響を受けなかった。

Effect of Capsianoside, a Diterpene Glycoside, on Tight-Junctional Permeability - PubMed
Previous work (Hashimoto et al., (1994) Biosci. Biotech. Biochem. 58, 1345) revealed that a sweet pepper extract enhanced the tight-junctional (TJ) permeability
スターアニス・紅茶

スターアニス(Illicium anisatum

紅茶(Camellia sinensis

リンデンTilia vulgaris)セイヨウシナノキ

クロツグ(Arenga engleri)

これらの抽出物はTEERを増加させた。

Modulations of Food-Derived Substances on Intestinal Permeability in Caco-2 Cell Monolayers - PubMed
The effects of more than 300 kinds of food extracts on intestinal permeability were investigated in Caco-2 cells with the use of model compounds: Lucifer Yellow
黒コショウ(ピペリン)

黒コショウ、ピーマンに含まれるピペリンによってイオン透過性の低下が引き起こされた。

ピーマン中の活性化合物はカプシアノシドとして同定され、これはアクチンフィラメントを再編成し、そしてTEERを減少させることが示された。

Effect of Capsianoside, a Diterpene Glycoside, on Tight-Junctional Permeability - PubMed
Previous work (Hashimoto et al., (1994) Biosci. Biotech. Biochem. 58, 1345) revealed that a sweet pepper extract enhanced the tight-junctional (TJ) permeability
Hot Spices Influence Permeability of Human Intestinal Epithelial Monolayers - PubMed
Indirect evidence suggests that hot spices may interact with epithelial cells of the gastrointestinal tract to modulate their transport properties. Using HCT-8
プレバイオティクス/繊維
イヌリン

イヌリンを濃縮させたパスタの投与群は、ゾヌリンを低下させ腸管バリア機能を維持した。

Inulin-enriched Pasta Improves Intestinal Permeability and Modifies the Circulating Levels of Zonulin and Glucagon-Like Peptide 2 in Healthy Young Volunteers - PubMed
Apart from the intestinal environment, inulin induces physiological effects, which includes a reduction in glucose and lipid concentrations and modulation of ga
ガラクトオリゴ糖

ガラクトオリゴ糖の投与は、ラットの腸管バリア機能を有意に改善する。

Protective Effect of Galactooligosaccharide-Supplemented Enteral Nutrition on Intestinal Barrier Function in Rats With Severe Acute Pancreatitis - PubMed
Supplementation of the prebiotic GOS in EN can significantly improve intestinal barrier function in SAP rats.
β-ラクトグロブリン

βラクトグロブリンは、ホエータンパク質の50%を占める不溶性のタンパク質。

βラクトグロブリンの投与はPKC阻害剤でTEERが減少した細胞を増加させた。

Effects of Beta-Lactoglobulin on the Tight-Junctional Stability of Caco-2-SF Monolayer - PubMed
The mechanisms for tight-junction (TJ) stabilization by beta-lactoglobulin (beta-Lg) were studied. Treatment of Caco-2-SF cells with inhibitors for some enzymes

ビタミン・栄養

ビタミンA

ビタミンAおよびその誘導体は腸管細胞の成長と分化を調節することが示されている。

ビタミンA欠乏は腸内細菌叢の変化を引き起こすことで腸管バリアを損なう。

Bacterial Population and Innate Immunity-Related Genes in Rat Gastrointestinal Tract Are Altered by Vitamin A-deficient Diet - PubMed
Vitamin A and its derivatives have been shown to regulate the growth and differentiation of gastrointestinal epithelial cells; in addition, vitamin A deficiency
Vitamin A Deficiency Exacerbates Methotrexate-Induced Jejunal Injury in Rats - PubMed
Two studies were conducted to investigate whether vitamin A-deficient rats were more susceptible to intestinal injury caused by methotrexate (MTX), since vitami
https://www.jstage.jst.go.jp/article/jnsv/56/6/56_6_347/_pdf
ビタミンC
The relationship between vitamin C status, the gut-liver axis, and metabolic syndrome
Metabolic syndrome (MetS) is a constellation of cardiometabolic risk factors, which together predict increased risk of more serious chronic diseases. …
ビタミンD

ランダム化比較試験 2000IU/日のビタミンD投与は、寛解期クローン病患者の腸管透過性を維持する。

Effects of Vitamin D Supplementation on Intestinal Permeability, Cathelicidin and Disease Markers in Crohn's Disease: Results From a Randomised Double-Blind Placebo-Controlled Study - PubMed
Short-term treatment with 2000 IU/day vitD significantly increased 25(OH)D levels in CD patients in remission and it was associated with increased LL-37 concent
Vitamin D, the gut microbiome and inflammatory bowel disease
Vitamin D has an important role in bone metabolism but recently has been recognized as an immunoregulator, and this has led to investigations on the effect of V
亜鉛

亜鉛欠乏はオクルディンの脱リン酸化およびβカテニン、ZO-1の過剰リン酸化を引き起こし、膜バリアの損傷を誘導した。培地が亜鉛で満たされた時これらは引き起こされなかった。

Zinc Deficiency Induces Membrane Barrier Damage and Increases Neutrophil Transmigration in Caco-2 Cells - PubMed
Zinc may contribute to the host defense by maintaining the membrane barrier. In this study, we questioned whether zinc deficiency affects the membrane function
グルタミン

グルタミンは透過性が増加したCaco-2細胞の回復させる。

Glutamine Supports Recovery From Loss of Transepithelial Resistance and Increase of Permeability Induced by Media Change in Caco-2 Cells - PubMed
Recent evidence suggests that the conditionally essential amino acid glutamine is important for intestinal barrier function. However, the mechanism remains unde
短鎖脂肪酸(SCFA)

酢酸塩、プロピオン酸塩、酪酸塩、吉草酸塩などの有機酸は、結腸内の未消化食物炭水化物の腸内微生物発酵によって産生される。

その中でも酪酸塩は腸管バリアを維持するための特別な役割を有している。酪酸塩の欠乏はタイトジャンクションでの病変を引き起こすが、補充はIBD(潰瘍性大腸炎)でのタイトジャンクションの回復に寄与し得る。

Microbial Butyrate and Its Role for Barrier Function in the Gastrointestinal Tract - PubMed
Butyrate production in the large intestine and ruminant forestomach depends on bacterial butyryl-CoA/acetate-CoA transferase activity and is highest when fermen

大腸炎のラットモデルの実験では、酪酸塩による治療がタイトジャンクションの完全性の維持およびTNFα放出の阻害と関連して、経上皮抵抗性の回復をもたらすことを示した。

Increased Permeability in Dextran Sulphate Colitis in Rats: Time Course of Development and Effect of Butyrate - PubMed
Increased mucosal permeability is a very early change in colitis induced by DSS, is accompanied by decreased cell survival, and precedes detectable changes in h

ハーブ

ケルセチン、フラボノイド

ブドウやタマネギに含まれるケルセチンなどのフラボノイドは、上皮細胞の上皮抵抗性やクローディン-4の発現を増加させラットの腸管バリア機能を増強した。

Barrier Effects of Nutritional Factors - PubMed
High dietary intake of fruits and vegetables is associated with a reduced disease risk. Therefore, clinical interest is growing in therapies based on dietary su
Effects of Quercetin Studied in Colonic HT-29/B6 Cells and Rat Intestine in Vitro - PubMed
The aim of this study was to analyze the influence of quercetin on intestinal barrier function using the human colonic epithelial cell line HT-29/B6 and rat sma

ケルセチンはクローディン-4発現を増加させ、上皮バリア機能を強化する。

Quercetin Enhances Epithelial Barrier Function and Increases claudin-4 Expression in Caco-2 Cells - PubMed
Quercetin is the most abundant flavonoid and is assumed to have positive effects on the gastrointestinal mucosa after dietary intake. The aim of the study was t

ケルセチンはオクルディン、オクルディン-2、クローディン-1、クローディン-4の発現を介して腸管バリア機能を強化する。

Quercetin Enhances Intestinal Barrier Function Through the Assembly of Zonula [Corrected] occludens-2, Occludin, and claudin-1 and the Expression of claudin-4 in Caco-2 Cells - PubMed
Dietary flavonoids provide various beneficial effects for our health. We investigated the promotive effects of quercetin and myricetin on the intestinal barrier
クルクミン

クルクミンの経口補給は、腸内細菌ではなく直接的にラットの腸管バリア機能を改善させる。

Oral Supplementation with Non-Absorbable Antibiotics or Curcumin Attenuates Western Diet-Induced Atherosclerosis and Glucose Intolerance in LDLR−/− Mice – Role of Intestinal Permeability and Macrophage Activation
Association between circulating lipopolysaccharide (LPS) and metabolic diseases (such as Type 2 Diabetes and atherosclerosis) has shifted the focus from Western

クルクミンは、ヘムオキシゲナーゼ-1(HO-1)をアップレギュレーションすることにより、腸管バリアの損傷を改善する。

Curcumin Ameliorates Hydrogen Peroxide-Induced Epithelial Barrier Disruption by Upregulating Heme oxygenase-1 Expression in Human Intestinal Epithelial Cells - PubMed
Cur protects human intestinal epithelial cells against H(2)O(2)-induced disruption of TJ and barrier dysfunction via the HO-1 pathway.

クルクミンはラットの腸管透過性を改善させた。

Curcumin, a Component of Turmeric, Efficiently Prevents Diclofenac Sodium-Induced Gastroenteropathic Damage in Rats: A Step Towards Translational Medicine - PubMed
There is a need to find/discover novel leads to treat complex and/or multi-factorial disease(s). Curcumin (CUR) is one of the promising lead molecules which nee

クルクミン投与はラットの腸粘膜組織構造を有意に改善しTNF-αを低下させた。

Curcumin Protects Against the Intestinal Ischemia-Reperfusion Injury: Involvement of the Tight Junction Protein ZO-1 and TNF-α Related Mechanism - PubMed
Present study aimed to investigate the eff ect of curcumin-pretreatment on intestinal I/R injury and on intestinal mucosa barrier. Thirty Wistar rats were rando

薬剤

メトホルミン

マウスの慢性的なフルクトース溶液の摂取はオクルディン、ZO-1の喪失と細菌内毒素の増加と関連しており、メトホルミン投与フルクトース誘発による脂肪症の発症を予防した。

Metformin Protects Against the Development of Fructose-Induced Steatosis in Mice: Role of the Intestinal Barrier Function - PubMed
To test the hypothesis that metformin protects against fructose-induced steatosis, and if so, to elucidate underlying mechanisms, C57BL/6J mice were either fed
カンナビス・サティバ

カンナビノイドは炎症誘発性腸管透過性に対して、相反する効果を有する。

テトラヒドロカンナビノール(THC)、カンナビジオールは、サイトカイン誘発性の増加した透過性に対する回復を加速させた。

一方でアナンダミド、2-アラキドニルグリセロールは、サイトカインの存在下でさらに透過性を増加させた。

PubMed
CB1R(腸カンナビノイド1型受容体)の活性化は(CB2Rではない)結腸の透過性に保護的役割を果たす。
Endogenous Cannabinoid System Regulates Intestinal Barrier Function in Vivo Through Cannabinoid Type 1 Receptor Activation - PubMed
The deleterious effects of stress on the gastrointestinal tract seem to be mainly mediated by the induction of intestinal barrier dysfunction and subsequent sub
メラトニン

メラトニン分泌の減少はアルコール中毒被験者の腸管透過性の増加と相関する。メラトニン補給は潜在的な治療法となる可能性がある。

Decreased melatonin secretion is associated with increased intestinal permeability and marker of endotoxemia in alcoholics
Chronic heavy alcohol use is known to cause gut leakiness and alcoholic liver disease (ALD), but only 30% of heavy drinkers develop increased intestinal permeab

 

プロバイオティクス

プロバイオティクス

プロバイオティクスによるタイトジャンクションの増加

Regulation of Tight Junction Permeability by Intestinal Bacteria and Dietary Components
Abstract. The human intestinal epithelium is formed by a single layer of epithelial cells that separates the intestinal lumen from the underlying lamina propri
Nissle 1917(EcN)
Escherichia coli Nissle 1917 - Wikipedia

プロバイオティック大腸菌 Nissle 1917(EcN)は、腸管病原性大腸菌株によるT84およびCaco-2細胞の感染によって引き起こされる腸バリアの破壊を防ぎ、タイトジャンクションと上皮バリアの修復をもたらす。

Molecular Mechanisms Underlying the Probiotic Effects of Escherichia Coli Nissle 1917 Involve ZO-2 and PKCzeta Redistribution Resulting in Tight Junction and Epithelial Barrier Repair - PubMed
The probiotic Escherichia coli strain Nissle 1917 (EcN) has been used for decades in human medicine in Central Europe for the treatment and prevention of intest
Probiotic Escherichia Coli Nissle 1917 Inhibits Leaky Gut by Enhancing Mucosal Integrity - PubMed
This study convincingly demonstrates that probiotic EcN is able to mediate up-regulation of ZO-1 expression in murine IECs and confer protection from the DSS co
Identification of Specific miRNAs Targeting Proteins of the Apical Junctional Complex That Simulate the Probiotic Effect of E. Coli Nissle 1917 on T84 Epithelial Cells - PubMed
In the intestine, dysregulation of miRNA is associated with inflammation, disruption of the gastrointestinal barrier, and the onset of gastrointestinal disorder

クローディン-14発現の増加

ビフィドバクテリウム・インファンティスY1

プロバイオティクス製品VSL#3の成分の1つであるビフィドバクテリウム・インファンティスY1によって分泌される代謝産物はZO-1とオクルディンの発現を増加させ、クローディン2の発現を減少させて経上皮抵抗性に対する効果を高め、イオン分泌を変えることにより、腸管透過性の改善をする。

Probiotic Bacteria Regulate Intestinal Epithelial Permeability in Experimental Ileitis by a TNF-dependent Mechanism - PubMed
Our data demonstrate that the previously established efficacy of VSL#3 in preventing SAMP ileitis is due to direct innate and homeostatic effects of TNF on the
Lactobacillus plantarum MB452

プロバイオティック株Lactobacillus plantarum MB452(VSL3プロバイオティック由来)は、オクルディンおよびシンギュリン遺伝子の転写を誘導することで、腸バリア機能を改善する可能性がある。

Lactobacillus Plantarum MB452 Enhances the Function of the Intestinal Barrier by Increasing the Expression Levels of Genes Involved in Tight Junction Formation - PubMed
This research indicates that enhancing the expression of genes involved in tight junction signalling is a possible mechanism by which L. plantarum MB452 improve
L.サリバリウス株UCC118 CCUG38008
Lactobacillus salivariusによる上皮バリア機能保護。
Mechanism of Protection of Transepithelial Barrier Function by Lactobacillus Salivarius: Strain Dependence and Attenuation by Bacteriocin Production - PubMed
Enhanced barrier function is one mechanism whereby commensals and probiotic bacteria limit translocation of foreign antigens or pathogens in the gut. However, b
L.ラムノサスGG
Lactobacillus rhamnosus GG
Lactobacillus Rhamnosus GG Culture Supernatant Ameliorates Acute Alcohol-Induced Intestinal Permeability and Liver Injury - PubMed
Endotoxemia is a contributing cofactor to alcoholic liver disease (ALD), and alcohol-induced increased intestinal permeability is one of the mechanisms of endot
ラクトバチルス・カゼイ株DN-114 001

プロバイオティクスLactobacillus casei DN-114 001の溶解物は、腸バリア機能を強化し、腸内微小環境を変化させることによって大腸炎を改善する。

Lysate of Probiotic Lactobacillus Casei DN-114 001 Ameliorates Colitis by Strengthening the Gut Barrier Function and Changing the Gut Microenvironment - PubMed
Our study provided evidence that even non-living probiotic bacteria can prevent the development of severe forms of intestinal inflammation by strengthening the
L.カゼイシロタ株
Lactobacillus Casei Shirota Protects From Fructose-Induced Liver Steatosis: A Mouse Model - PubMed
To test the hypothesis that Lactobacillus casei Shirota (Lcs) protects against the onset of non-alcoholic fatty liver disease (NAFLD) in a mouse model of fructo
Bifidobacterium lactis CNCM I-2494
Bifidobacterium lactis CNCM I-2494を含む市販発酵乳製品は、ラットの急性ストレスによって誘発される腸過敏症および結腸関門崩壊を抑制する。
A Marketed Fermented Dairy Product Containing Bifidobacterium Lactis CNCM I-2494 Suppresses Gut Hypersensitivity and Colonic Barrier Disruption Induced by Acute Stress in Rats - PubMed
This study illustrates that a probiotic food containing B. lactis CNCM I-2494 strain reduces visceral hypersensitivity associated with acute stress by normalizi
Lactobacillus brevis SBC8803

SBL88乳酸菌(学術名:Lactobacillus brevis SBC8803)が動物試験にて高い腸管バリア機能を持つ。

301 Moved Permanently
Lactobacillus paracasei A221

A221株は、クローディン-4の遺伝子発現量を増やすことにより、タイトジャンクションを強固にし、腸管上皮バリア増強作用を発揮することが示唆される。

Lactobacillus paracasei A221の腸管上皮バリア増強作用について
株式会社ナガセビューティケァのプレスリリース(2013年5月31日 11時30分)Lactobacillus paracasei A221の腸管上皮バリア増強作用について

プレバイオティクス

 

その他

糞便移植

クロストリジウム・ディフィシレ菌によって引き起こされる治療が困難な大腸炎に対して、糞便移植はよく反応する。

FDAは、C. difficileの治療においてのみ糞便移植の医学的利用を許可している。しかし実際には、多くの患者が深刻な腸内マイクロバイオームのかく乱により、他の治療法に十分に反応しないことから、多くの診療所が糞便移植の支援を行っている。

糞便移植の使用は、数割の患者が改善を示すが多くでは利益がなく、改善を示す患者と同数の患者が症状の悪化を報告している。明らかな問題はどの便が健康であるかをどういった方法で確認し、移植に使用できるかがわからないという点である。健康な糞便に含まれる構成成分は明確にはわかっていない。

また、糞便に含まれる可能性のあるすべての病原体を測定できるかどうかもわからない。糞便移植は輸血に似ている。血液が安全であるためにはドナーは健康でなければならないが 「健康な便」を見分ける技術はまだ限られており、安全なドナーの担保ができない。

胆汁
サイトカイン

IL-10、HB-EGF

Cytokine regulation of tight junctions
Epithelial and endothelial tight junctions act as a rate-limiting barrier between an organism and its environment. Continuing studies have highlighted the regul

腸内環境を改善させる因子の活性

アルカリフォスファターゼ活性

  • 黒胡椒
  • ピペリン
  • 赤唐辛子
  • カプサイシン
  • 生姜
  • 酪酸ナトリウム
  • 亜鉛
  • マグネシウム
  • カルシウム
  • クルクミン
  • オメガ3脂肪酸
  • ビタミンD
  • ビタミンK2
  • ラクトフェリン
  • L-グルタミン
  • フージュン茶(Fuzhuan tea )水溶性抽出物
  • ハーブ煎じ薬(Yu Ping Feng San)
  • ルチン(おそらく)
  • アピゲニン(おそらく)
  • チタン(ナノ粒子)
  • 二酸化ケイ素(ナノ粒子)
Intestinal Alkaline Phosphatase: Potential Roles in Promoting Gut Health in Weanling Piglets and Its Modulation by Feed Additives — A Review
The intestinal environment plays a critical role in maintaining swine health. Many factors such as diet, microbiota, and host intestinal immune response influen
(PDF) Curcumin and Chronic Kidney Disease (CKD): Major Mode of Action through Stimulating Endogenous Intestinal Alkaline Phosphatase
PDF | Curcumin, an active ingredient in the traditional herbal remedy and dietary spice turmeric (Curcuma longa), has significant anti-inflammatory... | Find, r
Recent advances in intestinal alkaline phosphatase, inflammation, and nutrition
Abstract. In recent years, much new data on intestinal alkaline phosphatase (IAP) have been published, and major breakthroughs have been disclosed. The aim of
Low Alkaline Phosphatase (ALP) In Adult Population an Indicator of Zinc (Zn) and Magnesium (Mg) Deficiency

アルカリフォスファターゼ低下・阻害

  • セージオイル
  • オレガノ油
  • L-フェニルアラニン(競合的阻害剤)
  • アスパルテーム
  • BCAA(非競合阻害剤)
  • 大豆種子貯蔵タンパク質b-コングリシニン(b-conglycinin)
Intestinal Alkaline Phosphatase: Potential Roles in Promoting Gut Health in Weanling Piglets and Its Modulation by Feed Additives — A Review
The intestinal environment plays a critical role in maintaining swine health. Many factors such as diet, microbiota, and host intestinal immune response influen

プレグナンX受容体アゴニスト

ビタミン類・栄養化合物
  • αリポ酸
  • ビタミンE
  • K2
  • リノレン酸
  • 胆汁酸
ハーブ類
  • グッグル
  • セントジョーンズワート
  • クルクミン
  • イチョウ葉
  • ケルセチン
  • ジインドリルメタン DIM(アブラナ科野菜)
  • 高麗人参(ジンセノサイドRb1)
  • バイカレイン
  • クローブ
  • ケンフェロール
  • クリシン
  • ピペリン
  • アルテミシニン(よもぎ)
  • タイム
ホルモン
  • プロゲステロン
  • プレグネノロン
  • コルチゾール
  • テストステロン
  • エストラジオール
  • T4、リバースT3
薬剤
  • ニコチン
  • リファンピシン
  • バルプロ酸
  • スピロノラクトン
  • ロバスタチン、シンバスタチン
  • フィナステリド

ファルネソイドX受容体(FXR)

作成中

腸管透過性を増加させる要因の回避

TEER = 経上皮電気抵抗 タイトジャンクションのバリア機能を評価する方法として広く用いられる。バリア機能が低下するとTEERの数値も低くなる。

食事・食材

大量の砂糖や脂肪

脂肪や炭水化物の多い西洋型の食事によって腸管透過性に顕著な影響が生じた。

A High-Fat Diet Is Associated With Endotoxemia That Originates From the Gut - PubMed
Endotoxemia, characterized by an excess of circulating bacterial wall lipopolysaccharide, is associated with systemic inflammation and the metabolic syndrome. P
高カロリー、西洋型の食事

カロリーの高い内毒素血症の増加と関連して高脂肪食は腸の透過性を高めた。

Metabolic Adaptation to a High-Fat Diet Is Associated With a Change in the Gut Microbiota - PubMed
The gut microbiota is a signature of the metabolic phenotypes independent of differences in host genetic background and diet.
Influence of a High-Fat Diet on Gut Microbiota, Intestinal Permeability and Metabolic Endotoxaemia - PubMed
Lipopolysaccharide (LPS) may play an important role in chronic diseases through the activation of inflammatory responses. The type of diet consumed is of major
フルクトース

食事に含まれる糖のうち、フルクトースが腸内細菌の過剰増殖と腸管透過性の増加と関連していることが示された。

Toll-like Receptor 4 Is Involved in the Development of Fructose-Induced Hepatic Steatosis in Mice - PubMed
Taken together, these data further support the hypothesis that in mice the onset of fructose-induced NAFLD is associated with intestinal bacterial overgrowth an
Serotonin Reuptake Transporter (SERT) Plays a Critical Role in the Onset of Fructose-Induced Hepatic Steatosis in Mice - PubMed
Elevated dietary fructose intake, altered intestinal motility, and barrier function may be involved in the development of nonalcoholic fatty liver disease (NAFL
小麦(グリアジン)

小麦などに含まれるグリアジンは、in vitroでオクルディンとZO-1の相互作用が損なわれ、細胞骨格が再構成され、単層透過性が増加する。

Gliadin, Zonulin and Gut Permeability: Effects on Celiac and Non-Celiac Intestinal Mucosa and Intestinal Cell Lines - PubMed
Based on our results, we concluded that gliadin activates zonulin signaling irrespective of the genetic expression of autoimmunity, leading to increased intesti

グリアジンはゾヌリンの分泌を誘導しPKCを介した細胞骨格の再編成を引き起こす。

Early Effects of Gliadin on Enterocyte Intracellular Signalling Involved in Intestinal Barrier Function - PubMed
Gliadin induces zonulin release in intestinal epithelial cells in vitro. Activation of the zonulin pathway by PKC mediated cytoskeleton reorganisation and tight
レクチン

レクチンは穀物、豆類、ナッツ、ジャガイモなどに含まれるタンパク質。

Modulation of Immune Function by Dietary Lectins in Rheumatoid Arthritis - PubMed
Despite the almost universal clinical observation that inflammation of the gut is frequently associated with inflammation of the joints and vice versa, the natu
Gliadin, Zonulin and Gut Permeability: Effects on Celiac and Non-Celiac Intestinal Mucosa and Intestinal Cell Lines - PubMed
Based on our results, we concluded that gliadin activates zonulin signaling irrespective of the genetic expression of autoimmunity, leading to increased intesti
中鎖脂肪酸(カプリン酸、ラウリン酸)

中鎖脂肪酸であるカプリン酸(C10)、ラウリン酸(C12)が、壁細胞の流動性を増加させた。

Absorption Enhancement Through Intracellular Regulation of Tight Junction Permeability by Medium Chain Fatty Acids in Caco-2 Cells - PubMed
Medium chain fatty acids (MCFAs) are used to enhance the permeability of mucosal tissues to hydrophilic drugs, but their mechanism of action is largely unknown.
DHA・γリノレン酸・EPA

 

トリプトファン
超生理学的なレベルのL‐トリプトファン食事補給は、ハムスター小腸上皮において細胞骨格および高分子透過性の変化を誘発する。
Supraphysiologic L-tryptophan Elicits Cytoskeletal and Macromolecular Permeability Alterations in Hamster Small Intestinal Epithelium in Vitro - PubMed
We have previously shown that Na(+)-coupled transport of glucose and amino acids across the apical membrane of intestinal absorptive cells is accompanied by alt
カイエンペッパー・パプリカ

カイエンペッパー、パプリカなどの香辛料はTEER(傍細胞イオン透過性の尺度である経上皮電気抵抗)を急激に低下させ、タイトジャンクションにおいて高分子の透過性を高めた。

Hot Spices Influence Permeability of Human Intestinal Epithelial Monolayers - PubMed
Indirect evidence suggests that hot spices may interact with epithelial cells of the gastrointestinal tract to modulate their transport properties. Using HCT-8
ホップ・マリーゴールド

300種類以上の食品抽出物から、腸の透過性に影響をおよぼす化合物のスクリーニング。以下の4つの抽出物がTEERを減少させた。

ホップ(Humulus lupulus

マリーゴールド(Tagetes erecta

ガランガルAlpinia officinarum)アジア料理で使われるショウガ科の植物

メグスリノキ(Acer nikoense ) 

Modulations of Food-Derived Substances on Intestinal Permeability in Caco-2 Cell Monolayers - PubMed
The effects of more than 300 kinds of food extracts on intestinal permeability were investigated in Caco-2 cells with the use of model compounds: Lucifer Yellow

 

薬剤

NSAID

NSAID治療を利用する患者の60~80%で、腸管バリア機能に問題が見られる。

NSIADの仕様による腸内細菌への影響と、その分解生成物が原因という一部の研究者の指摘がある。

Side Effects of Nonsteroidal Anti-Inflammatory Drugs on the Small and Large Intestine in Humans - PubMed
The adverse effects of NSAIDs distal to the duodenum represent a range of pathologies that may be asymptomatic, but some are life threatening.
https://www.ncbi.nlm.nih.gov/pubmed/12396306

IBS患者の腸管透過性は、NSAIDを摂取しなければ健常者と変わらない。

https://www.ncbi.nlm.nih.gov/pubmed/19255843

アセチルサリチル酸はNSAIDと対照的に、腸粘膜への損傷は少ない。

Clinicopathological Features of Nonsteroidal Antiinflammatory Drug-Induced Small Intestinal Strictures - PubMed
The clinicopathological features in 4 patients are described where nonsteroidal antiinflammatory drugs appear to have caused small intestinal strictures. Two pa
プロトンポンプ阻害薬

PPIが腸管バリア機能におよぼす影響のメカニズムは細胞死などによるものではなく、腸管透過性の調節作用によるものと考えられる。

303 See Other
Bacterial Infections in Cirrhosis: Role of Proton Pump Inhibitors and Intestinal Permeability - PubMed
Although in our animal model PPIs induced intestinal overgrowth, stage of liver disease rather than PPI use was the predominant factor determining infection ris

ライフスタイル

激しい運動

高強度、長時間の運動は迷走神経活動を低下させ腸管バリアの完全性を低下させる。

My Gut Feeling Says Rest: Increased Intestinal Permeability Contributes to Chronic Diseases in High-Intensity Exercisers - PubMed
Chronic diseases are the leading cause of death and disability worldwide, and many of these conditions are linked to chronic inflammation. One potential cause o

一晩の絶食後の激しい運動は、健康な若い男性の腸管透過性を増加させた。しかし一週間後に繰り返すと適応反応が見られた。

Adaptation of Exercise-Induced Stress in Well-Trained Healthy Young Men - PubMed
What is the central question of this study? Exercise is known to induce stress-related physiological responses, such as changes in intestinal barrier function.

持久力運動は、健康な男性の超透過性を増加させた。

Endurance Exercise Increases Intestinal Uptake of the Peanut Allergen Ara H 6 After Peanut Consumption in Humans - PubMed
Controlled studies on the effect of exercise on intestinal uptake of protein are scarce and underlying mechanisms largely unclear. We studied the uptake of the

軍人の戦闘訓練によるストレスは腸の透過性を変化させた。

Gastrointestinal Symptoms and Altered Intestinal Permeability Induced by Combat Training Are Associated With Distinct Metabotypic Changes - PubMed
Physical and psychological stress have been shown to modulate multiple aspects of gastrointestinal (GI) physiology, but its molecular basis remains elusive. We

長期間(4週間)の強い戦闘訓練は、兵士のストレス、不安を増加させるだけでなく、胃腸症状、免疫の活性、腸管透過性も増加させた。

Combat-training Increases Intestinal Permeability, Immune Activation and Gastrointestinal Symptoms in Soldiers - PubMed
Prolonged combat-training not only induces the expected increases in stress, anxiety and depression, but also GI symptoms, pro-inflammatory immune activation an

疾患

クローン病(CD)

 

炎症性腸疾患(IBD)
Polymorphisms in E-cadherin (CDH1) Result in a Mis-Localised Cytoplasmic Protein That Is Associated With Crohn's Disease - PubMed
The mis-localisation of E-cadherin and beta-catenin may explain the increased permeability seen in some patients with Crohn's disease. Thus, the polymorphisms i
Altered Permeability in Inflammatory Bowel Disease: Pathophysiology and Clinical Implications - PubMed
Barrier dysfunction in inflammatory bowel disease contributes to diarrhea by a leak flux mechanism and can cause mucosal inflammation secondary to luminal antig
過敏性腸症候群(IBS)
Irritable Bowel Syndrome: Methods, Mechanisms, and Pathophysiology. The Confluence of Increased Permeability, Inflammation, and Pain in Irritable Bowel Syndrome - PubMed
Irritable bowel syndrome (IBS) is one of the most common gastrointestinal ailments among those seeking health care for gastrointestinal disorders. Despite its p
Diarrhoea-predominant Irritable Bowel Syndrome: An Organic Disorder With Structural Abnormalities in the Jejunal Epithelial Barrier - PubMed
The jejunal mucosa of IBS-D patients displays disrupted apical junctional complex integrity associated with mast cell activation and clinical manifestations. Th

IBS患者においてZO-1の有意な減少

Impaired Intestinal Barrier Integrity in the Colon of Patients With Irritable Bowel Syndrome: Involvement of Soluble Mediators - PubMed
Our study shows that colonic soluble mediators are able to reproduce functional (permeability) and molecular (ZO-1 mRNA expression) alterations observed in IBS
セリアック病
A Distinctive 'Microbial Signature' in Celiac Pediatric Patients - PubMed
Overall, the results highlighted a peculiar microbial TTGE profile and a significant higher biodiversity in CD pediatric patients' duodenal mucosa. The possible
Intestinal Permeability in Coeliac Disease: Insight Into Mechanisms and Relevance to Pathogenesis - PubMed
Coeliac disease is a gut disease driven by an abnormal immune response towards dietary gluten in genetically susceptible individuals. Whether and, if so, how ab
炎症性腸疾患
Intestinal Inflammation Targets Cancer-Inducing Activity of the Microbiota - PubMed
Inflammation alters host physiology to promote cancer, as seen in colitis-associated colorectal cancer (CRC). Here, we identify the intestinal microbiota as a t
慢性関節リウマチ
The Microbiome and Rheumatoid Arthritis - PubMed
Humans are not (and have never been) alone. From the moment we are born, millions of micro-organisms populate our bodies and coexist with us rather peacefully f
ゾヌリン
Zonulin, a Newly Discovered Modulator of Intestinal Permeability, and Its Expression in Coeliac Disease - PubMed
We identified zonulin, a novel human protein analogue to the Vibrio cholerae derived Zonula occludens toxin, which induces tight junction disassembly and a subs

アレルギー性疾患

Changes in Faecal Microbiota of Infants With Cow's Milk Protein Allergy--A Spanish Prospective Case-Control 6-month Follow-Up Study - PubMed
Major differences have been found in gut microbiota between healthy and allergic children, and a possible association between allergy and altered microbiota pat
Altered Early Infant Gut Microbiota in Children Developing Allergy Up to 5 Years of Age - PubMed
A more diverse gut microbiota early in life might prevent allergy development and may be related to the previously suggested inverse relationship between allerg

栄養失調

Gut Barrier Function in Malnourished Patients - PubMed
Intestinal barrier function is significantly compromised in malnourished patients, but the clinical significance is unclear.

感染性下痢

Recent Advances and Remaining Gaps in Our Knowledge of Associations Between Gut Microbiota and Human Health - PubMed
The complex gut microbial flora harbored by individuals (microbiota) has long been proposed to contribute to intestinal health as well as disease. Pre- and prob

NAFLD

NASH

Dietary Fructose and Intestinal Barrier: Potential Risk Factor in the Pathogenesis of Nonalcoholic Fatty Liver Disease - PubMed
Worldwide, not only the prevalence of obesity has increased dramatically throughout the last three decades but also the incidences of co-morbid conditions such
Selective Increases of Bifidobacteria in Gut Microflora Improve High-Fat-Diet-Induced Diabetes in Mice Through a Mechanism Associated With Endotoxaemia - PubMed
Together, these findings suggest that the gut microbiota contribute towards the pathophysiological regulation of endotoxaemia and set the tone of inflammation f

2型糖尿病

肥満

サイトカイン

IL-1、IL-4、IL-6、IL-13、TGFβ?、HGF、PDGF

Cytokine regulation of tight junctions
Epithelial and endothelial tight junctions act as a rate-limiting barrier between an organism and its environment. Continuing studies have highlighted the regul
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